A novel anti-Ia monoclonal antibody which specifically enhances the corresponding T cell alloreactivity.

An anti-I-Ab monoclonal antibody, designated K14.83-11, was produced in a fusion between SP 2/0 Ag-14 myeloma cells and spleen cells from a B10.D2/n mouse primed in vivo against C57BL/10. Unlike other anti-I-Ab monoclonal antibodies thus far described, K14.83-11 was found to have a combination of features involving specificity, isotype, and function, unique among existing anti-I-A reagents. K14.83-11 exhibited a strong binding to the I-Ab gene product, with only slight cross-reactivity to the I-Ap/q family of allelic products and no reactivity towards I-Ak,d. When analyzed for isotype, K14.83-11 was found to be of a rare IgG3 isotype. With respect to biologic activity, K14.83-11 not only failed to produce the expected inhibition of specific anti-I-Ab T cell reactivity in vitro, but instead produced a striking enhancement of T cell responses against the I-Ab gene product. The possible relationship of IgG isotype and function was suggested when the immunoenhancing effect of K14.83-11 on reactive T lymphocytes was reversed to that of suppression with highly purified F(ab)2 fragments obtained by pepsin digestion.